Yale Center for Neuroscience and Regeneration Research at 22

In 1986, Dr. Stephen Waxman moved from Stanford to head Yale University’s Department of Neurology. From his work at Palo Alto VA Medical Center (VAMC), he was familiar with the Department of Veterans Affairs’ long-standing interest in nervous system injuries and repair. “And I wanted to make the VA Hospital in West Haven, a Yale affiliate, a hub of research at Yale. So I decided to put my money where my mouth was,” he says of his decision to establish a research lab for spinal cord injury and treatment lab on the Connecticut VAMC campus.

PVA was supportive, but the hospital lacked space to set aside for a lab. Waxman persuaded VA to lease the footprint of a building on its grounds to Yale, which erected the building. Knowing that Paralyzed Veterans of America (Paralyzed Veterans) shared the same goals as his fledgling Center for Neuroscience and Regeneration Research, Waxman turned to the organization for donor assistance, and the result has been a most successful partnership that has brought about many advances in the search for a cure for paralysis and treatments for spinal cord injury and disease (SCI/D).

Breakthroughs truly have since become the norm at the Center, which to date has received more than $4 million from Paralyzed Veterans for its research. As the Center turns 22, its scientists continue the investigations that are significantly changing our understanding of SCI/D.

“The leaders of Paralyzed Veterans of America are our heroes,” says Stephen Waxman, MD, PhD, the Center director. “They’re willing to fund the risky, best ideas that in the rest of the real world likely would not get funded. One dollar from Paralyzed Veterans is worth six from the government because each PVA dollar gives us flexibility to test risky new ideas, speed to do it now and stability.”

At any one time, the Center houses 30-40 researchers from diverse disciplines, including cellular and molecular biologists, pain physiologists, stem cell experts and animal behaviorists. “One of the biggest strengths of our program is teamwork and collaboration,” says Lakshmi Bangalore, PhD, assistant director for scientific communications. “Our research is very interactive and the mandate is that everybody works toward the same goal, which is to restore and preserve function in the injured nervous system.” Idea exchange is constant, whether in weekly meetings, seminars or impromptu hallway consults.

Waxman and associate director Jeffery Kocsis, PhD, note four particularly promising studies under way, including one investigating multiple sclerosis, one nervous system disease in which remissions are common. Scientists now know where almost every molecule goes during remission. The next step: “To learn all we can, in order to induce remissions and use this in treating MS and SCI,” Waxman says.

The Center also is developing neuroprotective techniques to save and even regenerate the tissue around injury sites. After SCI, a penumbra of nerve cells, surrounding the injury itself, aren’t dead but have been bruised and are potentially salvageable. “Can we protect that tissue?” Waxman asks. “The answer in experimental systems is yes.”

In cell-based approaches being pioneered by Kocsis, adult bone marrow stem cells have been introduced intravenously, crossed over and taken on reparative functions in cord and brain. A phase 1 study with human stroke victims showed that the procedure is safe, and while Drs. Kocsis and Waxman emphasize that this initial safety study was not blinded and must be repeated in a controlled and blinded study, it provides a hint that the procedure may possibly be efficacious. Researchers led by Kocsis also have transplanted cells from a George Bush-approved stem cell line; results show successful remyelination—regrowth of protective myelin—in the brain and spinal cord of experimental animals.

A fourth Center study under Waxman involves neuropathic pain. “Veterans have more than their share of nerve injuries,” he notes. “So we asked them, what would you like us to fix? One of the answers, front and center, is ‘chronic pain’ ”

Already researchers have identified a single gene that when mutated causes pain signaling nerve cells to become overactive. “This is the first time in humans a single molecule has been indicted as causing pain,” Waxman reports, adding that the same molecule causes pain after nerve injury, and that the Center is now working with drug companies to block this.

“Each month we learn something new about the injured nervous system, and we remind ourselves that our research can make a difference for real people. In a realistic sense, we are delivering hope,” he says, “and we learned that from Paralyzed Veterans.”